The goal of this study is to establish a rhesus monkey model using adult T cell depleted marrow as a method for inducing tolerance to donor antigen in transplanted offspring. The transplantation of hematopoietic stem cells (HSC) into an immunoincompetent fetal recipient may allow the creation of a permanent hematochimera without the risks of marrow ablation, rejection, and graft vs. host disease (GVHD) seen in postnatal BMT. The specific aims of this study are: 1) to establish in a rhesus monkey model the ability of in utero transplantation of T cell depleted parental marrow to induce lasting tolerance in the fetus and newborn to parental alloantigen; to characterize the state of tolerance induced in engrafted animals and the role of monocytes; to evaluate strategies for selective immunosuppression of the recipient to enhance engraftment and/or extend the time in gestation at which the fetus can be tolerized; and to determine whether the induced tolerance extends to vascularized grafts from the marrow donor. We plan to transplant T cell depleted parental marrow into 50-80 day fetal monkeys and define the optimal time to induce tolerance and the optimal stem cell dose. We will also evaluate the efficacy of anti T Cell monoclonal antibodies in extending the time at which the fetus is susceptible to tolerance induction and evaluate mechanisms for increasing the relative number of donor stem cells. Finally, we will study the mechanism for the induction of tolerance in engrafted animals and determine whether tolerance to allogeneic cells extends to vascularized kidney grafts from the marrow donor. The strategies and interventions developed in the fetal monkey will be directly applicable to the human and should result in improved treatment for many marrow stem cell defects and inborn errors of metabolism.